Skip to main content
SpringerLink
Log in

Trends and Issues in Characterizing Early Cognitive Changes in Parkinson’s Disease

  • Behavior (HS Kirshner, Section Editor)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

In this review, we first discuss trends and issues in measuring cognitive changes in PD, including recent efforts to define the diagnostic classification of “PD Mild Cognitive Impairment” (PD-MCI). After reviewing some limitations associated with this diagnosis, we discuss how measures derived from the neurocognitive sciences offer better precision in detecting early cognitive changes in PD. To support this idea, we highlight 2 influential lines of current investigation that are unveiling novel insights about specific cognitive processes that are vulnerable early in PD and of critical importance to clinicians involved in treating PD: action control and reward learning and decision making. We conclude by highlighting some extant issues and unresolved questions for future investigations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Hely MA, Reid WG, Adena MA, et al. The Sydney multicenter study of Parkinson's disease: the inevitability of dementia at 20 years. Mov Disord. 2008;23(6):837–44.

    Article  PubMed  Google Scholar 

  2. Aarsland D, Bronnick K, Larsen JP, et al. Cognitive impairment in incident, untreated Parkinson disease: the Norwegian ParkWest study. Neurology. 2009;72(13):1121–6.

    Article  PubMed  CAS  Google Scholar 

  3. Caviness JN, Driver-Dunckley E, Connor DJ, et al. Defining mild cognitive impairment in Parkinson's disease. Mov Disord. 2007;22(9):1272–7.

    Article  PubMed  Google Scholar 

  4. Janvin CC, Larsen JP, Aarsland D, Hugdahl K. Subtypes of mild cognitive impairment in Parkinson's disease: progression to dementia. Mov Disord. 2006;21(9):1343–9.

    Article  PubMed  Google Scholar 

  5. Dalrymple-Alford JC, Livingston L, MacAskill MR, et al. Characterizing mild cognitive impairment in Parkinson's disease. Mov Disord. 2011;26(4):629–36.

    Article  PubMed  Google Scholar 

  6. Fernandez HH, Crucian GP, Okun MS, et al. Mild cognitive impairment in Parkinson's disease: the challenge and the promise. Neuropsychiatr Dis Treatment. 2005;1(1):37–50.

    Article  Google Scholar 

  7. • Jellinger KA. Mild cognitive impairment in Parkinson disease: heterogenous mechanisms. J Neural Transm. 2012;Epub ahead of print. This is an excellent summary of the heterogeneous presentations and factors that result in a diagnosis of Mild cognitive Impairment in Parkinson's Disease.

  8. Litvan I, Goldman JG, Troster AI, et al. Diagnostic criteria for mild cognitive impairment in Parkinson's disease: Movement Disorder Society Task Force guidelines. Mov Disord. 2012;27(3):349–56.

    Article  PubMed  Google Scholar 

  9. Muslimovic D, Post B, Speelman JD, Schmand B. Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology. 2005;65(8):1239–45.

    Article  PubMed  Google Scholar 

  10. Troster AI. A precis of recent advances in the neuropsychology of mild cognitive impairment(s) in Parkinson's Disease and a proposal of preliminary research criteria. J Int Neuropsychol Soc. 2011;1–14

  11. Petersen RC, Smith GE, Waring SC, et al. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999;56(3):303–8.

    Article  PubMed  CAS  Google Scholar 

  12. Liepelt-Scarfone I, Graeber S, Feseker A, et al. Influence of different cut-off values on the diagnosis of mild cognitive impairment in Parkinson's disease. Parkinson's Dis. 2011;2011:540843.

    Google Scholar 

  13. Aarsland D, Bronnick K, Fladby T. Mild cognitive impairment in Parkinson's disease. Curr Neurol Neurosci Rep. 2011;11(4):371–8.

    Article  PubMed  Google Scholar 

  14. Cools R. Dopaminergic modulation of cognitive function-implications for L-DOPA treatment in Parkinson's disease. Neurosci Biobehav Rev. 2006;30(1):1–23.

    Article  PubMed  CAS  Google Scholar 

  15. Cools R, D'Esposito M. Inverted-U-shaped dopamine actions on human working memory and cognitive control. Biol Psychiatry. 2011;69(12):e113–25.

    Article  PubMed  CAS  Google Scholar 

  16. Cools R, Barker RA, Sahakian BJ, Robbins TW. Enhanced or impaired cognitive function in Parkinson's disease as a function of dopaminergic medication and task demands. Cereb Cortex. 2001;11(12):1136–43.

    Article  PubMed  CAS  Google Scholar 

  17. Costa A, Peppe A, Dell'Agnello G, et al. Dopaminergic modulation of visual-spatial working memory in Parkinson's disease. Dement Geriatr Cogn Disord. 2003;15(2):55–66.

    Article  PubMed  CAS  Google Scholar 

  18. Wylie SA, Claassen DO, Huizenga HM, et al. Dopamine agonists and the suppression of impulsive motor actions in Parkinson disease. J Cog Neurosci. 2012;24(8):1709–24.

    Article  Google Scholar 

  19. Obeso I, Wilkinson L, Jahanshahi M. Levodopa medication does not influence motor inhibition or conflict resolution in a conditional stop-signal task in Parkinson's disease. Exp Brain Res. 2011;213(4):435–45.

    Article  PubMed  CAS  Google Scholar 

  20. Ridderinkhoff KR, Forstmann BU, Wylie SA, Burle B, van den Wildenberg WPM. Neurocognitive mechanisms of action control: resisting the call of the Sirens. Wiley Interdisciplinary Rev Cogn Sci. 2011;2:174–92.

    Article  Google Scholar 

  21. Ridderinkhoff KR. Activation and suppression in conflict tasks: Empirical clarification through distributional analyses. In: Hommel WPB, editor. Common mechanisms in perception and action, attention, & performance. Oxford: Oxford University Press; 2002. p. 494–519.

    Google Scholar 

  22. Botvinick MM, Braver TS, Barch DM, et al. Conflict monitoring and cognitive control. Psychol Rev. 2001;108(3):624–52.

    Article  PubMed  CAS  Google Scholar 

  23. Gratton G, Coles MG, Donchin E. Optimizing the use of information: strategic control of activation of responses. J Exp Psychol Gen. 1992;121(4):480–506.

    Article  PubMed  CAS  Google Scholar 

  24. Aron AR. The neural basis of inhibition in cognitive control. Neuroscientist. 2007;13(3):214–28.

    Article  PubMed  Google Scholar 

  25. Casey BJ, Thomas KM, Welsh TF, Badgaiyan RD, Eccard CH, Jennings JR, et al. Dissociation of response conflict, attentional selection, and expectancy with functional magnetic resonance imaging. Proc Natl Acad Sci USA. 2000;97:8728–33.

    Article  PubMed  CAS  Google Scholar 

  26. Nee DE, Wager TD, Jonides J. Interference resolution: insights from a meta-analysis of neuroimaging tasks. Cogn Affect Behav Neurosci. 2007;7(1):1–17.

    Article  PubMed  Google Scholar 

  27. Davelaar EJ. A computational study of conflict-monitoring at two levels of processing: reaction time distributional analyses and hemodynamic responses. Brain Res. 2008;1202:109–19.

    Article  PubMed  CAS  Google Scholar 

  28. Forstmann BU, Jahfari S, Scholte HS, et al. Function and structure of the right inferior frontal cortex predict individual differences in response inhibition: a model-based approach. J Neurosci. 2008;28(39):9790–6.

    Article  PubMed  CAS  Google Scholar 

  29. Forstmann BU, van den Wildenberg WP, Ridderinkhof KR. Neural mechanisms, temporal dynamics, and individual differences in interference control. J Cog Neurosci. 2008;20(10):1854–65.

    Article  Google Scholar 

  30. Ridderinkhof KR, van den Wildenberg WP, Segalowitz SJ, Carter CS. Neurocognitive mechanisms of cognitive control: the role of prefrontal cortex in action selection, response inhibition, performance monitoring, and reward-based learning. Brain Cogn. 2004;56(2):129–40.

    Article  PubMed  Google Scholar 

  31. Eriksen BA, Eriksen CW. Effects of noise letters upon the identification of target letters in a non-search task. Percept Psychophys. 1974;16(1974):143–9.

    Article  Google Scholar 

  32. Simon JR. Reactions toward the source of stimulation. J Exp Psychol. 1969;81(1):174–6.

    Article  PubMed  CAS  Google Scholar 

  33. Simon JR. The effects of an irrelevant directional cue on human information processing. In: Proctor RW, Reeve TG, editors. Stimulus-response compatibility: An integrated perspective. Amsterdam: North-Holland; 1990. p. 31–63.

    Google Scholar 

  34. van den Wildenberg WP, Wylie SA, Forstmann BU, et al. To head or to heed? Beyond the surface of selective action inhibition: a review. Front Hum Neurosci. 2010;4:222.

    PubMed  Google Scholar 

  35. Praamstra P, Stegeman DF, Cools AR, Horstink MW. Reliance on external cues for movement initiation in Parkinson's disease. Evidence from movement-related potentials. Brain. 1998;121(Pt 1):167–77.

    Article  PubMed  Google Scholar 

  36. Wylie SA, Stout JC, Bashore TR. Activation of conflicting responses in Parkinson's disease: evidence for degrading and facilitating effects on response time. Neuropsychologia. 2005;43(7):1033–43.

    Article  PubMed  Google Scholar 

  37. Wylie SA, van den Wildenberg WP, Ridderinkhof KR, et al. The effect of Parkinson's disease on interference control during action selection. Neuropsychologia. 2009;47(1):145–57.

    Article  PubMed  CAS  Google Scholar 

  38. Wylie SA, Ridderinkhof KR, Bashore TR, van den Wildenberg WP. The effect of Parkinson's disease on the dynamics of on-line and proactive cognitive control during action selection. J Cogn Neurosci. 2010;22(9):2058–73.

    Article  PubMed  Google Scholar 

  39. Wylie SA, van den Wildenberg WP, Ridderinkhof KR, et al. The effect of speed-accuracy strategy on response interference control in Parkinson's disease. Neuropsychologia. 2009;47(8–9):1844–53.

    Article  PubMed  CAS  Google Scholar 

  40. Logan GD, Cowan WB, Davis KA. On the ability to inhibit simple and choice reaction time responses: a model and a method. J Exp Psychol Hum Percept Perform. 1984;10(2):276–91.

    Article  PubMed  CAS  Google Scholar 

  41. Gauggel S, Rieger M, Feghoff TA. Inhibition of ongoing responses in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry. 2004;75(4):539–44.

    PubMed  CAS  Google Scholar 

  42. van den Wildenberg WP, van Boxtel GJ, van der Molen MW, et al. Stimulation of the subthalamic region facilitates the selection and inhibition of motor responses in Parkinson's disease. J Cog Neurosci. 2006;18(4):626–36.

    Article  Google Scholar 

  43. Bonnin CA, Houeto JL, Gil R, Bouquet CA. Adjustments of conflict monitoring in Parkinson's disease. Neuropsychology. 2010;24(4):542–6.

    Article  PubMed  Google Scholar 

  44. Fielding J, Georgiou-Karistianis N, Bradshaw J, et al. No sequence dependent modulation of the Simon effect in Parkinson's disease. Brain Res Cogn Brain Res. 2005;25(1):251–60.

    Article  PubMed  Google Scholar 

  45. Praamstra P, Plat FM. Failed suppression of direct visuomotor activation in Parkinson's disease. J Cog Neurosci. 2001;13(1):31–43.

    Article  CAS  Google Scholar 

  46. Falkenstein M, Hoormann J, Christ S, Hohnsbein J. ERP components on reaction errors and their functional significance: a tutorial. Biol Psychol. 2000;51(2–3):87–107.

    Article  PubMed  CAS  Google Scholar 

  47. Gehring WJ, Goss B, Coles MGH, Meyer DE, Donchin E. A neural system for error detection and compensation. Psychol Sci. 1993;4(1993):385–90.

    Article  Google Scholar 

  48. Holroyd CB, Coles MG. The neural basis of human error processing: reinforcement learning, dopamine, and the error-related negativity. Psychol Rev. 2002;109(4):679–709.

    Article  PubMed  Google Scholar 

  49. Stemmer B, Segalowitz SJ, Dywan J, et al. The error negativity in nonmedicated and medicated patients with Parkinson's disease. Clin Neurophysiol. 2007;118(6):1223–9.

    Article  PubMed  Google Scholar 

  50. Willemssen R, Muller T, Schwarz M, et al. Error processing in patients with Parkinson's disease: the influence of medication state. J Neural Transm. 2008;115(3):461–8.

    Article  PubMed  CAS  Google Scholar 

  51. Wylie SA, Ridderinkhof KR, Elias WJ, et al. Subthalamic nucleus stimulation influences expression and suppression of impulsive behaviour in Parkinson's disease. Brain. 2010;133(Pt 12):3611–24.

    Article  PubMed  Google Scholar 

  52. Vandenbossche J, Deroost N, Soetens E, et al. Freezing of gait in Parkinson disease is associated with impaired conflict resolution. Neurorehabil Neural Repair. 2011;25(8):765–73.

    Article  PubMed  Google Scholar 

  53. Wylie S, van den Wildenberg WPM, Ridderinkhof KR, et al. Differential susceptibility to motor impulsivity among functional subtypes of Parkinson's disease. J Neurol Neurosurg Psychiatry. (In press)

  54. Schultz W. Dopamine neurons and their role in reward mechanisms. Curr Opin Neurobiol. 1997;7(2):191–7.

    Article  PubMed  CAS  Google Scholar 

  55. Hirsch E, Graybiel AM, Agid YA. Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease. Nature. 1988;334(6180):345–8.

    Article  PubMed  CAS  Google Scholar 

  56. Manes F, Sahakian B, Clark L, et al. Decision-making processes following damage to the prefrontal cortex. Brain. 2002;125(Pt 3):624–39.

    Article  PubMed  Google Scholar 

  57. Bechara A. Neurobiology of decision-making: risk and reward. Semin Clin Neuropsychiatry. 2001;6(3):205–16.

    Article  PubMed  CAS  Google Scholar 

  58. Poletti M, Frosini D, Lucetti C, et al. Iowa Gambling Task in de novo Parkinson's disease: a comparison between good and poor performers. Mov Disord. 2012;27(2):331–2.

    Article  PubMed  Google Scholar 

  59. Ibarretxe-Bilbao N, Junque C, Tolosa E, et al. Neuroanatomical correlates of impaired decision-making and facial emotion recognition in early Parkinson's disease. Eur J Neurosci. 2009;30(6):1162–71.

    Article  PubMed  Google Scholar 

  60. Perretta JG, Pari G, Beninger RJ. Effects of Parkinson disease on two putative nondeclarative learning tasks: probabilistic classification and gambling. Cogn Behav Neurol. 2005;18(4):185–92.

    Article  PubMed  Google Scholar 

  61. Deister CA, Teagarden MA, Wilson CJ, Paladini CA. An intrinsic neuronal oscillator underlies dopaminergic neuron bursting. J Neurosci. 2009;29(50):15888–97.

    Article  PubMed  CAS  Google Scholar 

  62. Schott BH, Minuzzi L, Krebs RM, et al. Mesolimbic functional magnetic resonance imaging activations during reward anticipation correlate with reward-related ventral striatal dopamine release. J Neurosci. 2008;28(52):14311–9.

    Article  PubMed  CAS  Google Scholar 

  63. Frank MJ, Seeberger LC, O'Reilly RC. By carrot or by stick: cognitive reinforcement learning in parkinsonism. Science. 2004;306(5703):1940–3.

    Article  PubMed  CAS  Google Scholar 

  64. Graef S, Biele G, Krugel LK, et al. Differential influence of levodopa on reward-based learning in Parkinson's disease. Front Hum Neurosci. 2010;4:169.

    Article  PubMed  Google Scholar 

  65. Voon V, Sohr M, Lang AE, et al. Impulse control disorders in Parkinson disease: a multicenter case–control study. Ann Neurol. 2011;69(6):986–96.

    Article  PubMed  Google Scholar 

  66. Claassen DO, van den Wildenberg WP, Ridderinkhof KR, et al. The risky business of dopamine agonists in Parkinson disease and impulse control disorders. Behav Neurosci. 2011;125(4):492–500.

    Article  PubMed  CAS  Google Scholar 

  67. Martinez-Horta S, Kulisevsky J. Is all cognitive impairment in Parkinson's disease "mild cognitive impairment"? J Neuroal Transm. 2011;118(8):1185–90.

    Article  Google Scholar 

  68. Voon V, Reynolds B, Brezing C, et al. Impulsive choice and response in dopamine agonist-related impulse control behaviors. Psychopharm. 2010;207(4):645–59.

    Article  CAS  Google Scholar 

  69. Zgaljardic DJ, Borod JC, Foldi NS, Mattis P. A review of the cognitive and behavioral sequelae of Parkinson's disease: relationship to frontostriatal circuitry. Cogn Behav Neurol. 2003;16(4):193–210.

    Article  PubMed  Google Scholar 

  70. Zgaljardic DJ, Borod JC, Foldi NS, et al. An examination of executive dysfunction associated with frontostriatal circuitry in Parkinson's disease. J Clin Exp Neuropsychol. 2006;28(7):1127–44.

    Article  PubMed  Google Scholar 

  71. Kahn E, D'Haese PF, Dawant B, et al. Deep brain stimulation in early stage Parkinson's disease: operative experience from a prospective randomised randomized clinical trial. J Neurol Neurosurg Psychiatry. 2012;83(2):164–70.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Claassen: American Academy of Neurology Clinical Research Training grant; Wylie: National Institute on Ageing grant; K23AG028750 (the content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Ageing or the National Institutes of Health).

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

  1. Department of Neurology, Vanderbilt University Medical Center, 1161 21st Avenue South, A-0118 Medical Center North, Nashville, TN, 37232, USA

    Daniel O. Claassen & Scott A. Wylie

Authors
  1. Daniel O. Claassen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Scott A. Wylie
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel O. Claassen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Claassen, D.O., Wylie, S.A. Trends and Issues in Characterizing Early Cognitive Changes in Parkinson’s Disease. Curr Neurol Neurosci Rep 12, 695–702 (2012). https://doi.org/10.1007/s11910-012-0312-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11910-012-0312-5

Keywords

Search

Navigation